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precision-medicine-therapeutics

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Precision Medicine Treatment Planning

Generate personalized treatment plans driven by pharmacogenomics, somatic and germline variant interpretation, and patient-specific clinical data. This skill integrates the Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines, ClinVar pathogenicity annotations, and PharmGKB drug-gene relationships to translate raw genomic data into actionable therapeutic recommendations.

Quick Install

npx skills add Open-Medica/open-medical-skills --skill precision-medicine-therapeutics

What It Does

  • Pharmacogenomic dosing guidance: Maps patient genotype results (e.g., CYP2D6 poor metabolizer, CYP2C19 rapid metabolizer) to CPIC-guideline dosing recommendations for over 400 drug-gene pairs
  • Variant-to-therapy matching: Cross-references somatic tumor variants against FDA-approved companion diagnostics and NCCN-recommended targeted therapies (e.g., EGFR mutations to osimertinib, BRAF V600E to vemurafenib/cobimetinib)
  • ClinVar and ClinPGx integration: Pulls current pathogenicity classifications and clinical significance annotations to contextualize genomic findings within treatment decisions
  • Multi-drug interaction overlay: After selecting genotype-guided therapies, screens the resulting regimen for drug-drug interactions using pharmacogenomic metabolism data
  • Structured treatment output: Produces treatment plans with gene-drug pairs, recommended dose adjustments, alternative agents, monitoring parameters, and supporting evidence citations

Clinical Use Cases

  • Antidepressant selection: A psychiatrist orders pharmacogenomic testing for a patient with treatment-resistant depression. The skill interprets CYP2D6 and CYP2C19 results and recommends escitalopram dose reduction for ultra-rapid CYP2C19 metabolizers or suggests switching to a non-CYP2D6-dependent agent
  • Oncology targeted therapy: A medical oncologist receives next-generation sequencing results showing an ALK rearrangement in a non-small cell lung cancer patient. The skill maps the variant to FDA-approved ALK inhibitors (crizotinib, alectinib, lorlatinib) with tier-level evidence annotations
  • Cardiology: Clopidogrel response: A cardiologist considering dual antiplatelet therapy post-PCI uses the skill to check CYP2C19 loss-of-function allele status and recommends prasugrel or ticagrelor for intermediate/poor metabolizers per CPIC guidelines
  • Pain management pharmacogenomics: Guides opioid selection by interpreting CYP2D6 status; flags codeine as contraindicated in ultra-rapid metabolizers due to rapid morphine conversion risk

Safety & Evidence

  • Safety Classification: Caution — Genomic interpretation directly influences prescribing decisions. All recommendations must be validated by a qualified clinician before implementation. The skill flags variants of uncertain significance (VUS) distinctly from pathogenic/likely pathogenic findings and does not recommend treatment changes based on VUS alone.
  • Evidence Level: High — Recommendations are grounded in CPIC guidelines (peer-reviewed, evidence-based), PharmGKB curated annotations, ClinVar submissions from expert clinical laboratories, and FDA pharmacogenomic labeling.

Example Usage

Pharmacogenomic dose adjustment:

Patient genotype: CYP2D6 *4/*4 (poor metabolizer)
Current medication: codeine 30mg Q4H PRN for pain
Recommend adjustment.

Result: CYP2D6 poor metabolizer status results in negligible conversion of codeine to its active metabolite morphine. Codeine will be ineffective for analgesia. CPIC guideline recommendation: avoid codeine entirely. Consider morphine, oxycodone (partially CYP2D6-dependent but has direct analgesic activity), or non-opioid alternatives based on pain severity.

Tumor variant therapy matching:

NGS results: BRAF V600E mutation detected in metastatic melanoma
No prior targeted therapy exposure
Recommend treatment options.

Result: BRAF V600E is an FDA-approved companion diagnostic biomarker. Recommended regimens: (1) Encorafenib + binimetinib (COLUMBUS trial, PFS 14.9 months); (2) Dabrafenib + trametinib (COMBI-d trial, PFS 11.0 months); (3) Vemurafenib + cobimetinib (coBRIM trial, PFS 12.3 months). Single-agent BRAF inhibitor monotherapy is not recommended due to inferior outcomes and rapid resistance via MAPK pathway reactivation.

Technical Details

  • Category: Treatment
  • Author: OMS Contributors
  • License: MIT
  • Version: 1.0.0
  • Specialty: Medical Genetics, Oncology, Pharmacology

References

  • Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines — cpicpgx.org
  • PharmGKB: Pharmacogenomics Knowledge Base — pharmgkb.org
  • ClinVar database (NCBI) — ncbi.nlm.nih.gov/clinvar/
  • Relling MV, Klein TE. "CPIC: Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network." Clin Pharmacol Ther. 2011;89(3):464-467.
  • NCCN Clinical Practice Guidelines in Oncology (current edition)
  • FDA Table of Pharmacogenomic Biomarkers in Drug Labeling

This skill is part of Open Medical Skills, a curated marketplace of medical AI skills maintained by physicians for physicians and the healthcare industry.